Temozolomide: a cytostatic drug that is still important today

IF 0.4 4区医学 Q4 PHARMACOLOGY & PHARMACY

Acta poloniae pharmaceutica Pub Date : 2023-03-03 DOI:10.32383/appdr/159449

Kamil Dyrka, A. Czarnywojtek, M. Borowska, Jeremi Kościński, J. Moskal, N. Sawicka-Gutaj, A. Lewandowska, S. V. Van Gool, M. Fichna, P. Gut, K. Pietrończyk, Patryk Graczyk, M. Dworacka

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引用次数: 0

Abstract

TMZ has an advantage over other traditional alkylating agents (carmustine, lomustine, procarbazine), which are highly toxic and have poor patient survival. TMZ circumvents these problems because cytochrome P450 enzymes and the kidneys are not involved in its metabolism, it has predictable side effects (nausea, vomiting, thrombocytopenia, neutropenia), which are usually reversible and only mild to moderate, have been widely described. About half of patients treated with TMZ have high drug resistance induced by activity of O6-methylguanine methyltransferase. Cancer stem cells (CSCs), which are found among the neoplastic cell population, have also been shown to be responsible for resistance to TMZ. Additionally, acquired immunity, induced by TMZ’s epigenetic and genetic alterations, may develop. Currently, there are new therapeutic strategies for GBM based on nanotechnology, which are aimed at improving TMZ treatment (e.g. the use of apolipoprotein), or other techniques (siRNA, which increases the oxygen level in the tumour). Thus, although TMZ was discovered more than three decades ago, this drug will be used to treat not only GBM, but also a large number of neoplastic pathologies. Further research focused on understanding the mechanisms of action and resistance to TMZ is required to improve its clinical application today and in the future. Keywords: alkylating agents, drug resistance, chemotherapy, nanoparticles, cancer, glioblastoma multiforme

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替莫唑胺：一种至今仍很重要的细胞抑制药物

TMZ比其他传统的烷化剂（卡莫司汀、洛莫司汀和普鲁卡嗪）具有优势，后者毒性高，患者存活率低。TMZ避开了这些问题，因为细胞色素P450酶和肾脏不参与其代谢，它具有可预测的副作用（恶心、呕吐、血小板减少症、中性粒细胞减少症），这些副作用通常是可逆的，仅为轻度至中度，已被广泛描述。大约一半接受TMZ治疗的患者具有由O6甲基鸟嘌呤甲基转移酶活性诱导的高耐药性。在肿瘤细胞群中发现的癌症干细胞（CSCs）也被证明对TMZ具有耐药性。此外，TMZ的表观遗传学和遗传改变可能诱导获得性免疫。目前，基于纳米技术的GBM有新的治疗策略，旨在改善TMZ的治疗（例如使用载脂蛋白）或其他技术（siRNA，提高肿瘤中的氧气水平）。因此，尽管TMZ是在30多年前发现的，但这种药物不仅将用于治疗GBM，还将用于治疗大量肿瘤病理。需要进一步研究TMZ的作用机制和耐药性，以提高其在当今和未来的临床应用。关键词：烷化剂，耐药性，化疗，纳米颗粒，癌症，多形性胶质母细胞瘤

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来源期刊

Acta poloniae pharmaceutica 医学-药学

CiteScore

0.80

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.